The placenta provides the physiological interface between mother and fetus and is critically involved in controlling the environment directing the development of the fetus. Trophoblast cells, the parenchymal cells of the placenta, form the framework of the gestational conduit that delivers resources to the fetus. Disruptions in the development of trophoblast cells result in retardation in the growth and maturation of the fetus. The objectives of this project are to understand control mechanisms involved in regulating trophoblast cell differentiation. In this proposal, our focus is directed towards identifying the regulatory mechanisms involved in identifying signaling pathways arising from the cell surface to the nucleus that are responsible for the development of trophoblast giant cells. Proposed studies utilize the rat chorioallantoic placenta and in vitro rat trophoblast cell culture systems. Two major specific aims, formulated as questions, are addressed in this research: 1) What is the nature of the intracellular signaling pathways involved in the control of trophoblast giant cell differentiation? 2) Is there a link between trans- acting factors and cis-elements controlling trophoblast giant cell- specific gene expression and the signaling pathways implicated in trophoblast giant cell differentiation? The experimentation utilizes molecular biology, protein chemistry, immunochemistry, and various cell biology and cell culture techniques. Identification of regulatory mechanisms controlling trophoblast cell differentiation will provide a better understanding of placental development and an avenue into the etiology of early pregnancy loss and various disorders and neoplasms of the placenta.